The purpose of this study is to examine the endocrine, immune and genetic parameters that may affect the development of spontaneous autoimmune thyroiditis in Obese strain chickens. Measurements will be made of sequential changes in circulating levels of thyroid hormone (T4,T3), development of defects in thyroidal hormonogenesis, alterations in serum free T4 and T3 and the appearance in serum of non-hormonal iodoproteins and iodothyronine-binding immunoglobulins. Ultrastructural studies will be made of the thyroid, pituitary, thymus, and bursa of Fabricius to detect changes in basement membranes. Studies of the immune response in OS chickens will examine hyperactive responses to autologous, homologous and heterologous antigens and to the growth of tumors. Other experiments will seek to determine if the heightened activity of B cells is due to a decrease in suppressor T cells or to an increase in helper T cells. Pathogenetic mechanisms of thyroid damage will be explored by examination of serum for the presence of immune complexes that might trigger cellular infiltration and tissue destruction. Cellular cytotoxitity in vitro will be examined for the action of K cells and serum antibody on thyroglobulin coated red blood cells. In vivo attempts will be made to restore an imbalance in T and B cell populations by trasfer of thymus cells, thymosin or by injection of levamisole to activate T cells. Another approach will be to determine if reactivity to self as reflected by autoimmune disease may depend upon the major histocompatibility complex at the B blood group locus. Lymphocytes will be chemically modified so that cytotoxicity measurements will provide an assessment of reactivity to modified self components.